(DOX) is a highly effective anti-neoplastic agent; however, its cumulative dosing schedules are clinically limited by the development of cardiotoxicity. Previous studies have attributed the cause of DOXmediated cardiotoxicity to mitochondrial iron accumulation and the ensuing reactive oxygen species (ROS) formation. The present study investigates the role of frataxin (FXN), a mitochondrial iron-sulfur biogenesis protein, and its role in development of DOX-mediated mitochondrial dysfunction. Athymic mice treated with DOX (5 mg/ kg, 1 dose/wk with treatments, followed by 2-wk recovery) displayed left ventricular hypertrophy, as observed by impaired cardiac hemodynamic performance parameters. Furthermore, we also observed significant reduction in FXN expression in DOX-treated animals and H9C2 cardiomyoblast cell lines, resulting in increased mitochondrial iron accumulation and the ensuing ROS formation. This observation was paralleled in DOX-treated H9C2 cells by a significant reduction in the mitochondrial bioenergetics, as observed by the reduction of myocardial energy regulation. Surprisingly, similar results were observed in our FXN knockdown stable cell lines constructed by lentiviral technology using short hairpin RNA. To better understand the cardioprotective role of FXN against DOX, we constructed FXN overexpressing cardiomyoblasts, which displayed cardioprotection against mitochondrial iron accumulation, ROS formation, and reduction of mitochondrial bioenergetics. Lastly, our FXN overexpressing cardiomyoblasts were protected from DOX-mediated cardiac hypertrophy. Together, our findings reveal novel insights into the development of DOX-mediated cardiomyopathy.anthracyclines; frataxin; cardiomyopathy; iron overload; mitochondrial damage; oxidative stress DOXORUBICIN (DOX) IS ONE OF the most widely used anti-neoplastic agents used for the treatment of a wide range of solid tumors and leukemia in children and adults (10,36,40). Despite its therapeutic usage, the clinical use of DOX is severely limited due to its cumulative dose-dependent cardiotoxicity, which develops over time into congestive heart failure (30). During this process, mitochondrial dysfunction has been observed to be fundamentally involved in the development of heart failure due to the dysregulation of mitochondrial bioenergetics and the generation of intracellular reactive oxygen species (ROS). The mechanism of DOX-induced cardiotoxicity at the cellular and subcellular levels is highly debatable. However, much attention has been attributed to the DOX-mediated formation of mitochondrial ROS. Although the role of iron has not been emphasized in the failing myocardial model, the role of iron in the formation of ROS has gained significance at the clinical setting with the usage of dexrazoxane (DXZ). DXZ, an iron chelator, is known to induce degradation of topo2␤ and prevent the DOX-mediated initiation of the DNA damage signal, H2AX-␥, in H9C2 cardiomyoblasts (28). However, the use of DXZ has been limited due to its interference with antitumor acti...

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Scutellaria lateriflora (American skullcap), a native plant of North America, has been used by Americans and Europeans as a nerve tonic for more than 200 years. In vivo studies have shown anxiolytic activity of S. lateriflora in animals and humans. However, the neuroprotective mechanisms of S. lateriflora are not fully understood. Oxidative stress plays a vital role in the neurodegenerative and neuropsychiatric diseases such as anxiety, Alzheimer's disease, depression, and Parkinson's disease. Bioactive compounds present in various medicinal plants neutralize or scavenge toxic free radicals and thus suppress oxidative stress. Therefore, the objective of this study was to investigate the antioxidant effects of S. lateriflora. The antioxidant potential of aqueous or ethanolic extracts of S. lateriflora was determined in mouse brain tissue using various biochemical assays. Protective effects of S. lateriflora against oxidative stress induced DNA fragmentation was determined using plasmid DNA. The ethanolic and aqueous extracts scavenged the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals. The ethanolic extract reduced tert-butyl peroxide-induced reactive oxygen species (ROS) and lipid peroxides in the mouse brain homogenates. Furthermore, the ethanolic extract of S. lateriflora protected hydrogen peroxide-UV induced cleavage of supercoiled plasmid DNA. In conclusion, S. lateriflora exhibited significant antioxidant effects. The current findings posit S. lateriflora as one of the potential experimental herbal drugs that should be screened for its therapeutic potential against various oxidative stress associated mental disorders.

Our study evaluated the immunomodulatory and performance properties of a nanotechnology‐based product Avian 3000® administered in drinking water to broilers. In this field trial, 48 broilers were selected from grower farms representing control and treated groups. Body and organ weights, feathering score, leg score, and bone density were the performance indicators. The immune response was assessed by measurement of serum alpha‐1‐acid glycoprotein (AGP), IgG, IgA and IgM concentrations.Statistically significant differences were not detected in any of the performance variables measured but among the organ weights, spleen weights approached significant difference between the two groups of broilers. Serum IgG and alpha‐1‐ acid glycoprotein concentration were found to be higher in the treated as compared to the untreated (P< 0.0003 and P<0.03, respectively) but serum IgM concentration was higher (P< 0.01) in the untreated birds. The groups did not differ in serum IgA (P>0.65) and total serum protein (P>0.11). The results indicate that Avian 3000® has immunomodulatory properties in chickens and controlled experiments are needed to reproduce and expand the findings.

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